Temporal and spatial expression of liver receptor homologue-1 (LRH-1) during embryogenesis suggests a potential role in gonadal development

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
Developmental Dynamics (Impact Factor: 2.38). 09/2005; 234(1):159-68. DOI: 10.1002/dvdy.20490
Source: PubMed


Liver receptor homologue-1 (LRH-1), an orphan member of the nuclear receptor family highly expressed in adult mouse ovary, is closely related to steroidogenic factor 1 (SF-1), known to be important in gonadal formation. To analyze the potential role of LRH-1 in gonadal differentiation, we compared LRH-1 and SF-1 expression during mouse embryonic and postnatal development. LRH-1 expression was first detected in the urogenital ridge before sexual determination, in primordial germ cells and surrounding somatic cells; expression persisted after differentiation into testes and ovaries. Of interest, LRH-1 expression declined in the developing ovary and testis at embryonic day 15.5 but increased again just after birth in the ovary in granulosa cells and transiently in oocytes of developing follicles. By comparing and contrasting LRH and SF-1 expression with the two tissue-specific steroidogenic markers, cytochromes P450 aromatase and P450 17alpha-hydroxylase/17,20 lyase, we provide evidence for a potential role for LRH-1 in gonadal development, the initiation of folliculogenesis and regulation of estrogen biosynthesis within the ovary.

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    • "Real-time PCR was performed to determine the level of expression of mRNA for Cyp17a1 (cytochrome P450, family 17, subfamily a, polypeptide 1) and Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1; aromatase) in the ovaries of each mouse that was sacrificed (Figure 1). Analysis of the level of mRNA for these two steroidogenic genes was used as another means of confirmation that the estrous cycle of each mouse had been staged correctly, as described by others (Soumano et al. 1996; Hinshelwood et al. 2005). Real-time PCR was performed using SYBR Green PCR Master Mix (Bio-Rad, Hercules, CA) and gene specific primer pairs (Cyp17a1 forward 5′-TGG TCA TAT GCA TGC CAA CT-3′ and reverse 5′-GAG CGT AGA CAG ATC TCG GG-3′; Cyp19a1 forward 5′-GTC CTG GCT ACT GTC TGG GA-3′ and reverse 5′-CAA ATG CTG CTT GAT GGA CT-3′) on a Bio- Rad IQ5 system, as described previously (Al-Alem et al. 2007; Bridges et al. 2010; Jeoung et al. 2010). "
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    • "The balance between cholesterol use in steroidogenesis and degradation in the bile acid pathway is not known, but most likely there is a fine balance which may prove crucial to oocyte maturation. In support of this hypothesis are recently published experimental data with rodents where a role for LRH-1 in steroidogenesis, gonadal development, aromatase expression, and progesterone biosynthesis was clearly documented [17], [28]. Another recent study has linked LRH-1 with ovulation in a rodent model, demonstrating that this receptor is required for rodent ovarian follicular development and fertility [17]. "
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The purpose of this study was to define novel diagnostic and prognostic factors for malignant gonadal germ cell tumors. In addition, the aim was to shed further light into the molecular mechanisms regulating gonadal germ cell tumorigenesis and differentiation by studying the roles of GATA transcription factors, pluripotent factors Oct-3/4 and AP-2γ, and estrogen receptors. This study revealed the prognostic value of CA-125 in malignant ovarian germ cell tumors. In addition advanced age and residual tumor had more adverse outcome. Several novel markers for histological diagnosis were defined. In the fetal development transcription factor GATA-4 was expressed in early fetal gonocytes and in testicular carcinoma precursor cells. In addition, GATA-4 was expressed in both gonadal germinomas, thus it may play a role in the development and differentiation of the germinoma tumor subtype. Pluripotent factors Oct-3/4 and AP-2γ were expressed in dysgerminomas, thus they could be used in the differential diagnosis of the germ cell tumors. Malignant ovarian germ cell tumors expressed estrogen receptors and their co-regulator SNURF. In addition, estrogen receptor expression was up-regulated by estradiol stimulation. Thus, gonadal steroid hormone burst in puberty may play a role in germ cell tumor development in the ovary. This study shed further light in to the molecular pathology of malignant gonadal germ cell tumors. In addition, some novel diagnostic and prognostic factors were defined. This data may be used in the differential diagnosis of germ cell tumor patients. Kivessyöpä on nuorten miesten yleisin kasvain. Näistä kasvaimista suurin osa on itusolukasvaimia ja niiden esiintyvyys on viimevuosina merkittävästi lisääntynyt. Munasarjan vastaavat pahanlaatuiset itusolukasvaimet ovat harvinaisia, mutta nuorilla fertiili-ikäisillä naisilla yleisiä kasvaimia. 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Munasarjan epiteliaalisen syövän diagnosoinnissa käytetty kasvainmerkkiaine CA-125 osoittautui ennusteelliseksi tekijäksi myös munasarjan itusolukasvaimissa. Pluripotentit tekijät AP-2gamma sekä Oct-3/4 ilmentyivät munasarjan dysgerminoomissa muiden alatyyppien ollessa negatiivisia näiden tekijöiden suhteen. Näitä merkkiaineita voidaan siten käyttää kasvainten histologiseen diagnosointiin. Transkriptiotekijä GATA-4 ilmentyi sikiön kehityksen aikana kiveksessä hyvin varhaisen vaiheen itusoluissa. Toisaalta GATA-4 ei ilmentynyt aikuisen kiveksen itusoluissa, mutta ilmentyi kiveskasvainten esiasteissa. GATA-4 ilmentyi myös molempien sukurauhasten germinooman tyypin kasvaimissa. GATA-4 tekijällä voi olla rooli kiveskasvainten esiasteiden synnyssä sekä kasvainten histologisessa erilaistumisessa. Munasarjan kaikki histologiset alatyypit ilmensivät estrogeeni-reseptoreita ja näiden säätelijää SNURF-proteiinia. 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